The proposal plan involves the study of an endogenous serine protease, plasminogen activator, (PA) and a detailed examination of its nature, function and role in the initiation persistence and maintenance of the malignant state. A procedure has been developed, using a tumor promotor and modified culture conditions, to obtain increased amounts of PA-enriched culture fluid from Rous sarcoma virus transformed chick fibroblasts (RSVCEF). Hence sufficient starting material for the eventual purification of RSVCEF PA is now available. An antibody against PA will be made and used as a direct probe to examine the cellular localization, processing, secretion, control and role of PA in malignant transformation. The proposed plan also involves the study of thrombin, a mitogenic, serine protease, and an examination of its mechanism of action in stimulating cell division. The thrombin studies serve as a model for examining growth control and cellular alternations by serine proteases.